The overall objective of the research proposed in this application is to determine the rheological and adherence properties of sickle blood cells and try to establish the relative contributions of these two factors to flow disruption and stasis in the microcirculation. In order to accomplish this objective, a series of experiments are designed with the following specific aims: 1) to differentiate between cell membrane and cytoplasmic effects in microrheological abnormalities of sickle blood; 2) to determine if the membrane is a structural site for damage in the disease, and to study the material origin of permanent membrane deformation in ISC formation; 3) to examine the potential for micro-occlusion as caused by red cell aggregation in plasma and/or adherence of blood cells to vascular endothelium. Direct micromechanical experiments will be used to measure the intrinsic viscoelastic and plastic properties of the red cell membrane, the aggregation potential of red cells in plasma, and the strength of red cell adherence to vascular endothelial cells. As these cellular properties appear to depend on red cell age and/or cell hemoglobin concentration, the experimental studies will be performed on oxygenated cells with specific MCHCs as established by density fractionation. Definition of these properties as a function of cell density and quantification of the proportions of red cells with various densities in whole blood of a selected group of patients with varying degrees of clinical severity, both in terms of vaso-occlusive phenomena and chronic anemia, may enable us to define the clinically important rheologic and adherence properties.